Orally administrable pharmaceuticals are mainly prescribed as oral solid pharmaceutical preparations such as tablets, powders, capsules, and the like. Among these preparations, tablets have been most often used at home and abroad because they can easily be administered and handled.
On the other hand, (2R)-2-propyloctanoic acid has been known to be a useful compound in a variety of diseases including cerebral apoplexy since it acts to improve the function of astrocytes (EP Patent 0632008 and EP-A-1174131). However, it was hard to formulate (2R)-2-propyloctanoic acid into such a formulation as tablets and to administer it to patients, because it is oil.
In general, it is considered preferable that the bulk drugs for pharmaceuticals, particularly the materials used as the bulk drugs for pharmaceuticals for oral solid preparations, are those obtained as crystals since the crystals allow a stable supply in large quantities and relatively easy formulation into such a form as tablets.
Accordingly, the materials which are intended to use as oral solid preparations are tried to crystallize by performing such an operation as formation of salts, when they are amorphous or liquid materials in a free state.
The above Patent Documents describe that (2R)-2-propyloctanoic acid may be formed into salts including salts with alkali metals (potassium, sodium, etc.), salts with alkaline earth metals (e.g., calcium, magnesium, etc.), ammonium salt, salts with organic amines (e.g., tetramethylammonium, triethylamine, methylamine, dimethylamine, cyclopentylamine, benzylamine, phenethylamine, piperidine, monoethanolamine, diethanolamine, tris(hydroxymethyl)amine, lysine, arginine, N-methyl-D-glucan, etc.), and the like.
The sodium salt of (2R)-2-propyloctanoic acid, i.e., alkali metal salt, however, was obtained not as crystals but as waxy solid in practical preparation; this was difficult to handle and had no desired physicochemical properties adaptable as a bulk drug for pharmaceuticals directed to oral solid preparations.
On the other hand, it is known that as for (2R)-2-propyloctanoic acid amine salts, a salt of (2R)-2-propyloctanoic acid with (R)-(+)-1-phenylethylamine can be obtained as a salt, which is used as an intermediate in production of optically highly pure (2R)-2-propyloctanoic acid (see: WO03/051852). The salts with other amines, however, have not yet been synthesized practically up to date; therefore, it was unclear whether it can be obtained as crystals and is endurable in use as a bulk drug for pharmaceuticals in oral solid preparations.